Honokiol augments the anti-cancer effects of oxaliplatin in colon cancer cells

Oxaliplatin is an important drug in the chemotherapy of colorectal carcinoma, but its toxicity, especially dose-related neurosensory toxicity, is not well tolerated. In this study, we investigated whether honokiol could augment the anti-tumor effect of oxaliplatin in colon cancer HT-29 cells in vitro and whether honokiol could be used with oxaliplatin to decrease oxaliplatin dose. We used the normal colon cells, human colonic epithelial cells (HCoEpiCs) as control cells. Cell proliferation, apoptosis, prostaglandin E2 (PGE(2)) and vascular endothelial growth factor (VEGF) levels were also investigated. Expression levels of cyclo-oxygenase 2 (COX-2), VEGF, AKT/p-AKT, extracellular signal-related kinase (ERK) 1/2/p-ERK1/2, nuclear factor kappa B (NF-kappa B) P65/p-P65, and caspase-3 were measured. Honokiol or oxaliplatin suppressed the proliferation of HT-29 cells in a concentration-dependent manner, but only high concentrations of honokiol would suppress the proliferation of HCoEpiCs. HT-29 cells were more sensitive to oxaliplatin treatment in the presence of honokiol. Oxaliplatin combined with honokiol improved the apoptosis rate of HT-29 cell and reduced PGE(2) and VEGF secretion levels. Expression levels of COX-2 and VEGF protein and phosphorylation of AKT, ERK1/2, and NF-kappa B P65 were also inhibited. Caspase-3 levels were upregulated after honokiol treatment. Therefore, honokiol can be used in combination with oxaliplatin in the chemotherapy of colon cancer. This combination allows a reduction in oxaliplatin dose, and thereby reduces its adverse effects. It may also enhance the chemotherapeutic effect of oxaliplatin for this disease.